Is CD93 p.Lys112Arg (c.335A>G) pathogenic?

CD93 p.Lys112Arg (c.335A>G) is classified Uncertain significance in CD93 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.0902); Ultra-rare (popmax 0.0752%, amr).

How common is CD93 p.Lys112Arg (c.335A>G) in the general population?

CD93 p.Lys112Arg (c.335A>G) is ultra-rare (popmax 0.0752%, amr) (gnomAD).

What do computational predictors say about CD93 p.Lys112Arg (c.335A>G)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

CD93 p.Lys112Arg

c.335A>G · rs750649569 · VCV2355235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0752%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -4.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 1.9, phastCons 0.94
Regional constraint	o/e 1.09	unconstrained · MANE · 2,239 bp · p 0.011 · regional, not allelic
Overall
CADD	15.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0752% Admixed American · 30/39,876 alleles

Filtering AF 0.0541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0469%

Overall 0.00774% 47/606,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0752%	1,329
European (non-Finnish)	0.00455%	21,969

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD93
Protein: p.Lys112Arg
Coding: c.335A>G
MANE Select: NM_012072
dbSNP: rs750649569
Type: single nucleotide variant
Location: chr20:23085858 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.07 · 2 PDB
Residue 112: the c-type lectin domain; a turn

Full CD93 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD93 p.Arg496= Benign/Likely benign ★★ same type
CD93 p.Gly448= Benign ★★ same type
CD93 p.His551= Likely benign ★★ same type
CD93 p.Pro541Ser Benign/Likely benign ★★ same type
CD93 p.Ser520Leu Benign ★★ same type
CD93 p.Thr493Ile Benign/Likely benign ★★ ⚠ same type
CD93 p.Val428Leu Benign ★★ same type
CD93 p.Ala214Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd93-p-lys112arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown